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Global analysis of S-nitrosylation sites in the wild type and APP transgenic mouse brain-clues for synaptic pathology

Zaręba-Kozioł, Monika and Szwajda, Agnieszka and Dadlez, Michal and Wysłouch-Cieszyńska, Aleksandra and Łałowski, Maciej (2014) Global analysis of S-nitrosylation sites in the wild type and APP transgenic mouse brain-clues for synaptic pathology. Molecular and Cellular Proteomics, 13 (9). pp. 2288-2305. ISSN 1535-9484

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Official URL: http://www.mcponline.org/content/13/9/2288.full.pd...

Abstract

Alzheimer’s disease (AD) is characterized by an early synaptic loss, which strongly correlates with the severity of dementia. The pathogenesis and causes of characteristic AD symptoms are not fully understood. Defects in various cellular cascades were suggested, including the imbalance in production of reactive oxygen and nitrogen species. Alterations in S-nitrosylation of several proteins were previously demonstrated in various AD animal models and patients. In this work, using combined biotinswitch affinity/nano-LC-MS/MS and bioinformatic approaches we profiled endogenous S-nitrosylation of brain synaptosomal proteins from wild type and transgenic mice overexpressing mutated human Amyloid Precursor Protein (hAPP). Our data suggest involvement of S-nitrosylation in the regulation of 138 synaptic proteins, including MAGUK, CamkII, or synaptotagmins. Thirty-eight proteins were differentially S-nitrosylated in hAPP mice only. Ninety-five S-nitrosylated peptides were identified for the first time (40% of total, including 33 peptides exclusively in hAPP synaptosomes). We verified differential S-nitrosylation of 10 (26% of all identified) synaptosomal proteins from hAPP mice, by Western blotting with specific antibodies. Functional enrichment analysis linked S-nitrosylated proteins to various cellular pathways, including: glycolysis, gluconeogenesis, calcium homeostasis, ion, and vesicle transport, suggesting a basic role of this post-translational modification in the regulation of synapses. The linkage of SNO-proteins to axonal guidance and other processes related to APP metabolism exclusively in the hAPP brain, implicates S-nitrosylation in the pathogenesis of Alzheimer’s disease. M

Item Type:Article
Additional Information:This research was originally published in Molecular & Cellular Proteomics. Zaręba-Kozioł, Monika and Szwajda, Agnieszka and Dadlez, Michal and Wysłouch-Cieszyńska, Aleksandra and Łałowski, Maciej (2014) Global analysis of S-nitrosylation sites in the wild type and APP transgenic mouse brain-clues for synaptic pathology. Molecular and Cellular Proteomics, 13 (9). pp. 2288-2305. ISSN 1535-9484 © the American Society for Biochemistry and Molecular Biology
Subjects:Q Science > Q Science (General)
Divisions:Mass Spectrometry Laboratory
ID Code:821
Deposited By: doctor Monika Zaręba-Kozioł
Deposited On:11 Dec 2014 09:54
Last Modified:08 Mar 2018 15:33

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